Effects of CGS 19755 and dizocilpine (MK 801) on delayed time discrimination performance.

The effects of the competitive NMDA (N-methyl-D-aspartate) receptor antagonist CGS 19755 and the non-competitive NMDA receptor antagonist dizocilpine (MK 801) on time discrimination and short-term memory were investigated in rats trained on a delayed time discrimination task. In a two-lever operant chamber, pressing one lever was correct and reinforced with a food pellet after presentation of a stimulus light for 2 s (S(short)D); pressing the opposite lever was correct after presentation of a stimulus light for 8 s (S(long)D). CGS 19755 (3.0 mg/kg) attenuated performance, decreased nose-pokes (an activity necessary to trigger the presentation of the discriminative stimulus and the presentation of the response levers), and increased response latencies (time from 'opportunity to leverpress' to 'actual leverpress'). The highest dose of dizocilpine (0.2 mg/kg) tested also attenuated performance. Further, the number of nose-pokes and response latencies were not altered by any dose of dizocilpine. With increasing delays, saline-injected animals developed a bias towards reporting an occurrence of an S(long)D, independent of the actual stimulus presented. This bias was attenuated or even reversed by CGS 19755 (3.0 mg/kg) and (0.2 mg/kg). Our results suggest that NMDA receptors are directly or indirectly involved in time discrimination performance.